This work is investigating several aspects of pancreatic islet transplantation in animals. During the past year we have concentrated on investigating new forms of immunosuppression to prevent the rejection of allogeneic islets. Total lymphoid irradiation and cyclosporin A have been tested in the rat heart allograft model. The treatment schedules that were nost effective have been tested in the more difficult pancreas and islet transplant models. Low dose TLI plus low dose cyclosporin A are synergistic and are highly effective. Preservation of islet tissue is also a major aspect of these experiments, and has been investigated in the dog autograft model. We have found cold storage for 24 hours and machine preservation for 24 hours to be effective with transplantation of immediately vascularized segmental grafts. Islets will be prepared for transplantation from pancreatic segments stored for this period of time. Metabolic studies on islet autotransplant dogs have shown that normal carbohydrate homeostasis cannot be completely achieved using one donor to one recipient. Experiments during the coming year will combine two imperfect techniques--islet autotransplantation and constant insulin infusion with an implantable pump--in an attempt to restore normal carbohydrate metabolism.